XA bacterial virulence protein promotes pathogenicity by inhibiting the Bacterium's Own F1Fo ATP synthase

Eun-Jin Lee, Mauricio H. Pontes, Eduardo A. Groisman

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Several intracellular pathogens, including Salmonella enterica and Mycobacterium tuberculosis, require the virulence protein MgtC to survive within macrophages and to cause a lethal infection in mice. We now report that, unlike secreted virulence factors that target the host vacuolar ATPase to withstand phagosomal acidity, the MgtC protein acts on Salmonella's own F 1Fo ATP synthase. This complex couples proton translocation to ATP synthesis/hydrolysis and is required for virulence. We establish that MgtC interacts with the a subunit of the F1F o ATP synthase, hindering ATP-driven proton translocation and NADH-driven ATP synthesis in inverted vesicles. An mgtC null mutant displays heightened ATP levels and an acidic cytoplasm, whereas mgtC overexpression decreases ATP levels. A single amino acid substitution in MgtC that prevents binding to the F1Fo ATP synthase abolishes control of ATP levels and attenuates pathogenicity. MgtC provides a singular example of a virulence protein that promotes pathogenicity by interfering with another virulence protein.

Original languageEnglish
Number of pages1
JournalCell
Volume154
Issue number1
DOIs
Publication statusPublished - 2013 Jul 3
Externally publishedYes

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Bacterial Proteins
Virulence
Bacteria
Adenosine Triphosphate
Salmonella
Protons
Proteins
Vacuolar Proton-Translocating ATPases
Salmonella enterica
Macrophages
Virulence Factors
Pathogens
Amino Acid Substitution
Mycobacterium tuberculosis
Acidity
NAD
Hydrolysis
Cytoplasm
Substitution reactions
Display devices

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

XA bacterial virulence protein promotes pathogenicity by inhibiting the Bacterium's Own F1Fo ATP synthase. / Lee, Eun-Jin; Pontes, Mauricio H.; Groisman, Eduardo A.

In: Cell, Vol. 154, No. 1, 03.07.2013.

Research output: Contribution to journalArticle

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